Zugaib João, Ceballos Cesar C, Leão Ricardo M
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto SP, Brazil.
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto SP, Brazil.
Hear Res. 2016 Feb;332:188-198. doi: 10.1016/j.heares.2015.10.008. Epub 2015 Nov 5.
High doses of salicylate induce reversible tinnitus in experimental animals and humans, and is a common tinnitus model. Salicylate probably acts centrally and induces hyperactivity in specific auditory brainstem areas like the dorsal cochlear nucleus (DCN). However, little is known about the effect of high doses of salicylate in synapses and neurons of the DCN. Here we investigated the effects of salicylate on the excitability and evoked and spontaneous neurotransmission in the main neurons (fusiform, cartwheel and tuberculoventral) and synapses of the DCN using whole cell recordings in slices containing the DCN. For this, we incubate the slices for at least 1 h in solution with 1.4 mM salicylate, and recorded action potentials and evoked and spontaneous synaptic currents in fusiform, cartwheel (CW) and putative tuberculoventral (TBV) neurons. We found that incubation with salicylate did not affect the firing of fusiform and TBV neurons, but decreased the spontaneous firing of cartwheel neurons, without affecting AP threshold or complex spikes. Evoked and spontaneous glutamatergic neurotransmission on the fusiform and CW neurons cells was unaffected by salicylate and evoked glycinergic neurotransmission on fusiform neurons was also unchanged by salicylate. On the other hand spontaneous glycinergic transmission on fusiform neurons was reduced in the presence of salicylate. We conclude that high doses of salicylate produces a decreased inhibitor drive on DCN fusiform neurons by reducing the spontaneous firing of cartwheel neurons, but this effect is not able to increase the excitability of fusiform neurons. So, the mechanisms of salicylate-induced tinnitus are probably more complex than simple changes in the neuronal firing and basal synaptic transmission in the DCN.
高剂量水杨酸盐可在实验动物和人类中诱发可逆性耳鸣，是一种常见的耳鸣模型。水杨酸盐可能作用于中枢，诱导特定听觉脑干区域（如背侧耳蜗核，DCN）的活动亢进。然而，关于高剂量水杨酸盐对DCN突触和神经元的影响知之甚少。在此，我们使用包含DCN的脑片全细胞记录技术，研究了水杨酸盐对DCN主要神经元（梭形、车轮状和结核腹侧神经元）及其突触的兴奋性、诱发和自发神经传递的影响。为此，我们将脑片在含有1.4 mM水杨酸盐的溶液中孵育至少1小时，并记录梭形、车轮状（CW）和假定的结核腹侧（TBV）神经元的动作电位、诱发和自发突触电流。我们发现，水杨酸盐孵育不影响梭形和TBV神经元的放电，但减少了车轮状神经元的自发放电，而不影响动作电位阈值或复合动作电位。水杨酸盐对梭形和CW神经元细胞的诱发和自发谷氨酸能神经传递没有影响，对梭形神经元的诱发甘氨酸能神经传递也没有改变。另一方面，在水杨酸盐存在的情况下，梭形神经元上的自发甘氨酸能传递减少。我们得出结论，高剂量水杨酸盐通过减少车轮状神经元的自发放电，降低了对DCN梭形神经元的抑制驱动，但这种作用并不能增加梭形神经元的兴奋性。因此，水杨酸盐诱发耳鸣的机制可能比DCN中神经元放电和基础突触传递的简单变化更为复杂。
